Fenebrutinib again bests Aubagio in trial at cutting MS relapse rates
Genentech will use these, other data to seek therapy's approval
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- Fenebrutinib, a treatment candidate for MS, significantly reduced relapse rates compared with the approved drug Aubagio in two clinical trials.
- The investigational BTK inhibitor also matched Ocrevus in slowing disability progression for primary progressive MS.
- Genentech plans to seek the therapy's approval for both relapsing MS and PPMS.
Fenebrutinib, Genentech’s investigational BTK inhibitor, was found to significantly reduce relapse rates compared with the approved therapy Aubagio (teriflunomide) in two Phase 3 clinical trials involving people with relapsing forms of multiple sclerosis (MS).
Positive top-line results from one of those trials, FENhance 2 (NCT04586023), were announced late last year. Now, Genentech has reported that its twin trial FENhance 1 (NCT04586010) also met its main goal. In both studies, fenebrutinib reduced relapse rates by more than 50% relative to Aubagio over about two years of treatment, the data show.
Genentech also previously announced that a separate Phase 3 trial called FENtrepid (NCT04544449) met its main goal in people with primary progressive multiple sclerosis (PPMS). In that study, fenebrutinib was shown to be at least as effective as the approved therapy Ocrevus (ocrelizumab) at slowing confirmed disability progression.
The company said it plans to use data from these trials to seek regulatory approvals of fenebrutinib for both relapsing forms of MS and PPMS. If approved, fenebrutinib would become the first oral therapy authorized for both indications, according to the developer.
“Fenebrutinib has the potential to become the first and only high-efficacy oral, brain-penetrant treatment for both [relapsing] MS and PPMS, showing a profound benefit on relapsing and progressive disease biology,” Genetech stated in a company press release announcing the latest trial findings.
As of now, the only therapies approved in the U.S. for both relapsing forms of MS and PPMS are Ocrevus — administered by infusion into the bloodstream — and its subcutaneous, or under-the-skin, formulation Ocrevus Zunovo (ocrelizumab and hyaluronidase-ocsq).
As an oral therapy, given as tablets, fenebrutinib is expected to ease treatment burden for some MS patients if approved for use.
Trials together tested fenebrutinib in nearly 1,500 with relapsing MS
MS is driven by inflammatory immune responses that damage nerve cells in the brain and spinal cord. Fenebrutinib aims to tamp down this inflammation by decreasing the activity of certain immune cells, particularly B-cells and microglia. The therapy specifically works to inhibit an immune cell protein called BTK.
The FENhance 1 and FENhance 2 studies together enrolled nearly 1,500 people with relapsing forms of MS. Each participant was randomly assigned to receive either fenebrutinib or Aubagio for nearly two years.
The main goal was to show that fenebrutinib is better than Aubagio at preventing relapses, and both trials met this endpoint. According to the company, fenebrutinib reduced relapse rates by 51% in FENhance 1 compared with Aubagio, and by 59% in FENhance 2.
Based on the observed relapse rates, which were not disclosed, Genentech stated that a person treated with fenebrutinib would experience, on average, one relapse approximately every 17 years.
These pivotal results, together with the earlier data, provide convincing evidence that fenebrutinib can become the first high-efficacy oral treatment for [relapsing MS] and PPMS.
Fenebrutinib is not the first BTK inhibitor to advance into Phase 3 clinical testing in relapsing MS, but it is the first in this class to demonstrate the ability to reduce relapse rates compared with Aubagio in large late-stage trials.
“These pivotal results, together with the earlier data, provide convincing evidence that fenebrutinib can become the first high-efficacy oral treatment for [relapsing MS] and PPMS,” said Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, a member of the Roche group.
8 patient deaths reported with fenebrutinib, 1 with Aubagio
Regarding safety in the FENhance studies, cases of liver enzyme elevations, a sign of liver damage that’s been reported with other BTK inhibitors, were comparable with fenebrutinib and Aubagio. Also, one patient on Aubagio died, whereas eight deaths were reported in patients on fenebrutinib, according to Genentech.
The company said the deaths among patients on fenebrutinib had “various causes” and occurred “at different points in treatment.”
“Further analyses are ongoing to better understand these findings,” per Genentech.
Detailed results from the FENhance trials are scheduled to be presented at the 2026 American Academy of Neurology Annual Meeting in April.
“Building on a decade of transforming MS treatment, we are committed to advancing innovation to one day allow people with MS to live a life without disability,” Garraway said.
